In subjects with severe insulin resistance, hirsutism and acanthosis nigricans, the relationship of the three components and basis of the insulin resistance remains undefined. In vivo insulin action is assessed by glucose and insulin tolerance tests as well as the euglycemic clamp. In vitro studies of insulin action in cultured fibroblasts from these subjects will evaluate possible intrinsic genetic defects in insulin action. The interaction of insulin and androgens in vivo and in vitro are explored.